The indirect evidence is mounting that folic acid may be playing some previously unsuspected role in brain functions governing mood and affect, and perhaps in disease states, including depression and schizophrenia. Our proposed studies of folate in mouse brain may have relevance to this interesting possibility. We have found that the synaptic region (synaptosomes) of mouse brain contains large amounts of folic acid coenzyme forms. We shall continue our study of the subcellular localization of folate forms, utilizing microbiological assays (L. casei and S. faecalis) after separation of subcellular particulates by differential centrifugation and sucrose gradient centrifugation. When the localization and characterization studies are completed we shall examine the turnovers of folates within these compartments by following the time course of radiolabeled folate entry and exit in vivo. We shall also continue our studies on the localization of folate conjugase of flutamyl synthetase, of serine transhydroxymethylase, homocysteine methyl tetrahydrofolate methyl transferase, and methylene tetrahydrofolate reductase. After the regional and subcellular localization studies and the turnover studies are completed, we shall examine the effects upon folates of the administration of agents known to affect the state of behavior.